刀豆蛋白A诱导小鼠实验性肝肾共损伤模型的建立  

Establishment of Simultaneous Liver and Kidney Lesion Model Induced by Concanavalin A in Mice

作　　者：崔佳丽[1,2] 山丽梅[1] 张萍[1] 王伽伯[1] 李宝才[2] 肖小河[3] 

机构地区：[1]解放军302医院全军中医药研究所,北京100039 [2]昆明理工大学生命科学与技术学院,昆明650224 [3]解放军302医院中西医结合医学中心,北京100039

出　　处：《中国实验方剂学杂志》2012年第22期210-214,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家公益性行业科研专项基金项目(200807020);军队后勤科研项目(司科专201089)

摘　　要：目的:筛选并初步建立能够诱导小鼠肝肾同时损伤的实验动物模型,为评价肝肾损伤治疗药物提供实验动物模型。方法:考察尾静脉注射刀豆蛋白A(Con A)10,15,20,40 mg·kg-1,造模时间12 h;ig给药D-半乳糖胺(D-Gal)1 g·kg-1及腹腔注射0.3%四氯化碳(CCl4,20 mL·kg-1)60 mg·kg-1,造模时间24 h;药物对模型小鼠肝脏、肾脏的损伤作用,通过检测肝肾功能相关的生化指标,肝脏及肾脏病理组织学改变,确定有效的造模方案。为进一步确定该模型是否能有效评价治疗肝肾损伤药物的药效,考察了大黄甘草汤对小鼠肝肾损伤模型的保护作用。结果:给予小鼠1 g·kg-1D-Gal,CCl460 mL·kg-1造模后,其血清直接胆红素(DBIL)、总胆红素(TBIL)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性与对照组比较均显著升高(P<0.05或P<0.01),而尿素氮(BUN)、肌酐(CRE)、总胆固醇(TC)、甘油三脂(TG),血清总蛋白(TP)、白蛋白(ALB)含量无明显变化,组织病理变化与血清生化指标结果相同,说明上述两种药物可诱发小鼠肝损伤模型,但未检测到肾损伤相关生化指标及病理变化;给予小鼠Con A 20 mg·kg-1造模后,小鼠血清DBIL,TBIL,ALT,AST,BUN,TC,TG,CRE,TP,ALB值与对照组相比较差异显著(P<0.01,P<0.05),说明Con A 20 mg·kg-1可诱发小鼠肝肾同时损伤,进一步优化模型,确定15 mg·kg-1Con A为诱发小鼠肝肾损伤的最佳剂量;给予模型验证方药大黄甘草汤干预后,肝肾损伤小鼠的生化和组织学检查均有显著改善。结论:初步建立尾静脉注射Con A 15 mg·kg-1诱导小鼠实验性肝肾同时损伤模型,用大黄甘草汤验证说明模型建立成功。Objective： To screen and establish the experimental animal model of simultaneous liver and kidney lesion in mice, and to provide experimental animal models for screening drugs which used to cure kidney and liver damage. Method： We investigated the damage effect of concanavalin A （Con A） , D-galactosamine （D- Gal） and carbon tetrachloride （CC14 ） in the mouse liver and kidney, and we established the effective modeling method by determing the biochemical indicators and the histopathological changes related to the liver and kidney function. To further inspect if the model is able to effectively evaluate the efficacy of drugs for kidney and liver damage, we study the protective effect of Dahuang Gancao decoction on liver and kidney damage using the established model. Result： 1 g .kg-1 D-Gal, CC14 （60 mg.kg-1） could induce liver injury in mice, but there is no evident about the renal injury; 20 mg.kg-1 Con A could induce liver and kidney damage simultaneously, and we determine the best dose of Con A to built simultaneous liver and kidner damage model as 15 mg.kg-1 after further optimization. The biochemical index and histological examination of kidney and liver damage mice were significantly improved after giving the prescription Dahuang Gancao decoction. Conclusion： We initially established the experimental model of simultaneous liver and kidney damage by injecting Con A 15 mg.kg-1 through tail vein, and proved to be successful by verification of Dahuang Gancao docoction.

关 键 词：肝肾损伤 动物模型 刀豆蛋白A 大黄甘草汤 

分 类 号：R285.5[医药卫生—中药学]